There is compelling evidence that many mutagens and carcinogens are able to react with cellular DNA either directly or following metabolic activation to reactive metabolites. If DNA replication proceeds on such a modified template before altered bases or nucleotides are removed by enzymic repair processes, the mutations can be genetically fixed. Thus, the extent of carcinogen-induced promutagenic DNA damage and the capacity of cells to repair such damage represent critical events in the initiation of carcinogenesis. We are studying the in vivo formation and repair of carcinogen metabolite-DNA adducts in target and non-target tissues for carcinogen-induced neoplasia, with emphasis on benzo(a)pyrene. We are concerned with the effect of dose of carcinogen and inhibitors of carcinogenesis on the amount and type of adducts formed. We are concerned with the adduct dose and time after carcinogen exposure on the excision repair of bulky adducts. Emphasis is on studies which enhance our understanding of the relationship between metabolism of carcinogen and the amounts and types of DNA adducts formed in the various tissues.